Glaucoma, one of the leading causes of blindness, is a disease characterized by decrease in visual field resulted from injury to optic nerves caused by aging or negative lifestyle habits, for example stressful environment.
Elevated intraocular pressure has been regarded as a major risk factor for developing glaucoma. Light entered through the crystalline lens of an eye is captured by the light receptors in retina, and biosignals given off by such phenomenon are transmitted to optic nerves in the retina. Then, the biosignals are transmitted to the brain through the optic nerve head located at the back of the eye, where the optic nerves are bundled. Development of high-tension glaucoma due to elevated intraocular pressure involves several stages. The first stage involves gradual injury to the optic nerves in the retina caused by atrophia and enlargement thereof, followed by the next stage which involves apoptosis of the retinal ganglion cells (RGCs), a type of neuron located in the retina. Then, it leads excavation of the optic nerve head that causes gradual decrease in visual field which eventually causes blindness. Several lines of evidence have been gradually accumulating from recent studies of high-tension glaucoma that suggest several risk factors such as ischemia, high glutamate intake and genetic background which play important roles in the pathogenesis and development of glaucoma. Furthermore, autoimmunity that directly recognizes retinal proteins has been associated with developing glaucoma.
Although the risk factor remains unknown, glaucoma occurs even at normal intraocular pressure with high frequency. In normal-tension glaucoma, clinical findings of (1) intraocular pressure within the range of normal level (10 to 21 mmHg), (2) constriction and excavation of optic nerve head periphery, (3) loss of a retinal nerve fiber layer, (4) metamorphosis and backward deviation of the optic nerve at lamina cribrosa (lamina orbital's) and (5) decrease in retinal ganglion cells and glial cells can be clinically and comprehensively observed, and normal-tension glaucoma is characterized by the specific lesions of the optic nerves.
Similar to high-tension glaucoma, normal-tension glaucoma also involves stages of atrophia and enlargement of the retinal ganglion cells, apoptosis of the retinal ganglion cells and excavation of the optic nerve head that causes gradual decrease in visual field which eventually causes blindness. The morbidity of normal-tension glaucoma patients in Japan is high. In fact, the morbidity thereof in the total population is said to be several percentage. In particular, 1 in 28 people (3.6%) aged 40 or over is a normal-tension glaucoma patients. Moreover, in elder patients aged 40 or over, mail or female, the morbidity of normal-tension glaucoma significantly increases with age. Although the morbidity of normal-tension glaucoma in people under the age of 40 is only approximately 0.1%, the morbidity increases to slightly fewer than 2% in 40s, slightly more than 2% in 50s, about 6% in 60s and about 7% in 70s or older. Normal-tension glaucoma is the second leading cause of blindness in Japan after diabetic retinopathy, but the pathogenesis and pathogenic mechanism thereof remain unknown. Therefore, there is no fundamental treatment for narrowed visual field caused by the development of normal-tension glaucoma. Consequently, allopathy using ophthalmic drug such as a sympatholytic drug, a sympathomimetic drug, a parasympathomimetic drug, a prostaglandin-related drug and a carbonic anhydrase inhibitor is performed to decrease the intraocular pressure.
To study pathogenic mechanism of normal-tension glaucoma or to develop therapeutics, a therapeutic agent, a preventive method or a preventive agent thereof, a normal-tension glaucoma model capable of developing conditions similar to distinctive chronic conditions of human normal-tension glaucoma which age-dependently occur more frequently and further develop in people at the age of 40 or older is desired.
In Japanese unexamined patent publication No. 2004-313188, an animal model of normal-tension glaucoma prepared by administering an aluminum compound thereto to induce injury to optic nerve axons is disclosed. However, according to this animal model, the injury is forcibly induced by the external drug administration, and thus the animal model is not capable of spontaneously developing the injury. Moreover, the animal model does not develop the injury age-dependently.